Pressure container for driving a medical device

ABSTRACT

The present disclosure relates to a portable pressure container for driving a medical device. The container includes a pressure housing confining an interior volume and a pressure outlet extending through the pressure housing . The interior volume comprises a liquid storage portion and a gas storage portion. The liquid storage portion and the gas storage portion are in flow connection with each other. The liquid storage portion is configured to store a liquid phase of a driving medium. The gas storage portion is configured to store a gas phase of the driving medium. The pressure outlet is only in flow connection with the gas storage portion.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of U.S. patentapplication Ser. No. 15/571,691, filed Nov. 3, 2017, which is thenational stage entry of International Patent Application No.PCT/EP2016/060146, filed on May 6, 2016, and claims priority toApplication No. EP 15166871.2, filed on May 8, 2015, the disclosures ofwhich are expressly incorporated herein in entirety by referencethereto.

TECHNICAL FIELD

The present disclosure relates to the field of pressure containers andin particular to pressure containers for pressure driven medical devicessuch like automatic injection devices for delivery of a liquidmedicament by way of injection.

BACKGROUND

Automatic medicament delivery devices, such like auto-injectors providea rather easy and convenient approach to inject a predefined dose of aliquid medicament into biological tissue. Such drug delivery devices mayprovide an injection needle extension and retraction mechanism in orderto puncture biological tissue to which the liquid medicament is to bedelivered. After the injection needle has been extended into aninjection position, drug delivery through the injection needle mayautomatically start. After termination of a delivery process the needleis typically retracted back into the housing. Since such drug deliverydevices are intended for home or self-medication, their general handlingshould be easily understandable and unambiguous.

Additionally, such devices should provide a high degree of patientsafety in order to avoid stitch damages or similar injuries. Thetherapy, the medication schedule, the size of the dose, and/or theviscosity of the liquid medicament may cause some difficulties andproblems with existing drug delivery device designs. For instance, thetotal time for the delivery of the medicament may be out of a predefinedrange. This can occur, in some cases, when the injection volume israther large, e.g., larger than 1.25 ml and/or when the liquidmedicament has a high viscosity. Alternatively, a high viscosity and alarge volume of the liquid medicament could lead to patient discomfort.

When such drug delivery or injection devices are of portable or mobiletype, they are typically equipped with some kind of energy storage toconduct a dispensing procedure and optionally to displace and to retractthe injection needle. Document US 2012/0071829 A1 describes an apparatusfeaturing a medicament injector moveably disposed within a housing andan energy storage member configured to produce a force to move themedicament injector to an injection position in which a portion of aneedle is disposed outside of a distal end portion of the housing.

The energy storage member is a compressed gas cylinder that is operableto produce a force that acts upon the medicament container to move themedicament container between a first position and a second position. Inresponse to a force produced by the pressurized gas, a moveable memberand the medicament injector are moved towards a distal end portion ofthe housing, thereby exposing the needle from the housing. Thereafter amovable member continues to move a medicament container distally withina carrier. This continued movement of the medicament container placesthe needle in fluid communication with the medicament container, therebyallowing the medicament to be injected. Finally, the force from thepressurized gas causes the movable member to move within the medicamentcontainer, thereby expelling the medicament through the needle.

Energy storage by compressed gas comes along with some limitations inregards to the stability of the pressure of the gaseous driving mediumas the compressed gas leaves the respective pressure container.Providing a constant pressure of the gaseous driving medium over arather long time interval, e.g. over a complete time of injection eitherrequires implementation of rather highly pressurized pressure containersor requires an increase of the size and the filling volume of suchpressure containers. For mobile or portable medical applications both ofthese options come along with some drawbacks in regards to compact andsmall-sized portable medical devices or in view of patient safety andhandling comfort.

SUMMARY

In a first aspect, a portable pressure container for driving a medicaldevice is provided. The container comprises a pressure housing confiningor defining an interior volume. The pressure container further has apressure outlet extending through the pressure housing. The pressureoutlet provides a flow or fluid connection between the exterior and theinterior volume of the pressure housing. Typically, the pressure outletcomprises some kind of standardized adapter or connector by way of whichthe pressurized content of the pressure container can be guided ortransferred to the medical device for driving the same.

The interior volume of the pressure housing comprises a liquid storageportion and a gas storage portion. The liquid storage portion and thegas storage portion are in flow connection with each other. Hence, aliquid phase of a driving medium located inside the liquid storageportion is free to evaporate into the gas storage portion and viceversa. Furthermore, the liquid storage portion is configured to store aliquid phase of a driving medium. In the same or similar way, the gasstorage portion is configured to store a gas phase of the drivingmedium.

Typically, the interior volume of the pressure housing is substantiallydivided into the liquid storage portion and the gas storage portion. Thedriving medium is typically located inside the interior volume of thepressure housing, wherein its liquid phase is predominantly locatedinside the liquid storage medium and wherein its gas phase is typicallyprovided in and completely fills the gas storage portion. Depending onthe pressure and temperature inside the pressure housing the liquidphase and the gas phase of the driving medium are in a state ofequilibrium. By modifying at least one of the pressure and thetemperature the equilibrium can be arbitrarily shifted so that forinstance at least 50 wt. % or more of the total driving medium ispresent in a liquid phase inside the pressure housing.

Moreover the pressure outlet of the portable pressure container is onlyor exclusively in flow connection with the gas storage portion of theinterior volume. In this way, it is substantially guaranteed and assuredthat only the gas phase of the driving medium may leave the pressurecontainer for driving the medical device, while the liquid phase of thedriving medium is substantially hindered from leaving the pressurecontainer.

With the portable pressure container to accommodate a liquid phase and agas phase of a driving medium a rather constant driving pressure can beprovided at the pressure outlet. As soon as the gas phase starts toemanate from the pressure housing via the pressure outlet a portion ofthe liquid phase of the driving medium evaporates into the gas phase. Asa result, a rather constant gas pressure can be obtained at the pressureoutlet for a comparatively long period of time. A rather constant gaspressure can be effectively provided at the pressure outlet as long asthere is sufficient liquid phase of the driving medium inside theinterior volume.

Typically, the portable pressure container is dedicated to be carriedalong by the patient thereby being thermally coupled to the patient. Forinstance, the medical device and hence the respective portable pressurecontainer may be adhesively attached to the skin of the patient. Then,an enthalpy of evaporation of the driving medium from the liquid phaseinto the gas phase can be compensated by an inherent supply of thermalenergy from the body of the patient, e.g. by way of the body heat of thepatient. Moreover, it is also conceivable that the quantity of theliquid phase exceeds the quantity typically needed to drive the medicaldevice. Then it is even conceivable that evaporation enthalpy isbranched off from the liquid phase of the driving medium, therebyexperiencing a slight cooling down as the gas phase escapes from thepressure container.

Having the pressure outlet exclusively in flow connection with the gasstorage portion is beneficial to provide an orientation-independentextraction of the gaseous phase from the portable pressure container.From a technical point of view, the flow of the gaseous phase emanatingfrom the pressure container is much easier to handle or to controlcompared to a liquid phase. Moreover, by way of storing a liquid phaseto evaporate into a gas phase the working volume and hence the drivingcapability of the driving medium can be increased multiple times. Bymaking use of a phase transition from a liquid phase towards a gas phasethe storage capability in terms of providing a propellant gas can beincreased without the necessity to increase the size of the portablepressure container.

According to another embodiment, the liquid storage portion is locatedremote and at a predefined non-zero distance from the pressure outlet.In addition, the gas storage portion is located between the liquidstorage portion and the pressure outlet. In this way, the driving mediume.g. predominately provided in the liquid phase inside the interiorvolume first has to undergo a phase transition from the liquid phaseinto the gas phase. For this and depending on the various conceivableembodiments and geometries of gas storage portion and liquid storageportion, the liquid phase must be provided at or near a phase transitionboundary between the liquid storage portion and the gas storage portion.Then, the liquid phase may at least partially or successively undergo aphase transition into the gas phase thereby maintaining a predefined gaspressure and an equilibrium inside the gas storage portion.

Arranging the gas storage portion between the liquid storage portion andthe pressure outlet, prevents a portion of the liquid phase of thedriving medium from entering the pressure outlet. In this way, the gasstorage portion provides a geometric separation between the liquidstorage portion and the pressure outlet.

The separation of the interior volume between the liquid storage portionand the gas storage portion may be of static or dynamic type. Whenimplemented as a static separation at least one of the liquid storageportion and the gas storage portion comprises a geometrical structurethat is particularly adapted to store only one of the liquid phase orthe gas phase of the driving medium. When implemented dynamically it isconceivable, that the liquid storage portion and the gas storage portionare separated by a movable boundary whose geometric structure depends ona momentary position of the liquid phase and the gas phase. It isconceivable, that the boundary between the liquid phase and the gasphase is sensitive to gravity so that the boundary between liquid phaseand gas phase is subject to dynamical changes as the orientation of thepressure container is modified.

In typical embodiments wherein the boundary between the liquid phase andthe gas phase is of dynamic type, it is of particular benefit when thevolume of the liquid phase of the driving medium is less than 60%, lessthan 50%, less that 40% or less than 30% of the interior volume of thepressure container. In this way it can be guaranteed that only the gasstorage portion is in flow connection with the pressure outlet.

According to a further embodiment, a porous storage medium or a poroustransport medium is arranged inside the liquid storage portion andextends towards or into the gas storage portion. When arranging a porousstorage medium inside the interior volume, the entire liquid storageportion of the pressure container may be filled with or may even bedefined by the porous storage medium. Typically, the porous storagemedium is selected such, that the pores and the capillary attractionarising therefrom are configured to soak up or to absorb a major portionor even the entirety of the liquid phase of the driving medium. An outeredge or outer surface of the porous storage medium then defines theboundary between the liquid storage portion and the gas storage portion.Having a major portion of the driving medium absorbed in the porousstorage medium inherently provides an orientation-independent extractionof the gaseous phase. Moreover, by making use of a porous storage mediumthe effective surface of the boundary between the liquid phase and thegas phase can be increased compared to an embodiment, wherein thesurface of a filling level of the liquid phase defines said boundary.

When making use of a porous storage medium inside the interior volume itis the outer geometry and the surrounding volume of the porous storagemedium that effectively defines the liquid storage portion of theinterior volume. Typically, the residual portion of the interior volumethen defines the gas storage portion.

In embodiments wherein a porous transport medium is located inside theinterior volume, the transport medium is in flow connection with theliquid phase of the driving medium. It may be, for instance, immersedinto the liquid phase of the driving medium. The porous transport mediumis then at least with one end in fluid communication or in physicalcontact with the liquid phase whereas another end is in contact with orextends towards the gas storage portion.

With such an embodiment, it is generally conceivable to divide theliquid storage portion and the gas storage portion of the interiorvolume by a division structure, such like a division wall. It is then ofparticular benefit, when the division structure or division wall isintersected by the porous transport medium, thereby supporting awell-defined transport of the liquid phase of the driving medium out ofthe liquid storage portion and towards or into the gas storage portion.With such embodiments it is of particular benefit, when the poroustransport medium extends almost through the entire liquid storageportion so that one end of the elongated porous transport medium isstill in fluid connection with the liquid phase even if a considerableamount of the liquid phase has already left the liquid storage portion.An opposite end of the porous transport medium then typically extendsinto an evaporation chamber, which is either a portion of the gasstorage portion or which is in direct flow communication with the gasstorage portion.

According to a further embodiment, the porous storage medium is inabutment with an inner side of the pressure housing. In this way, theporous storage medium can be fixed to the pressure housing so as toprovide a well-defined position and geometry of the liquid storageportion. By arranging the porous storage medium to an inner side, e.g.to a bottom portion or sidewall portion of the pressure housing, athermal contact as well as a heat transfer from the exterior towards theporous storage medium can be improved. Moreover, by fixing and arrangingthe porous storage medium to the inside of the pressure housing a mutualcontact between the pressure outlet and the porous storage medium, thatcould potentially lead to a clogging of the pressure outlet lead to canbe effectively prevented.

According to another embodiment, the porous storage medium and thepressure outlet are arranged in or at opposite end sections of thepressure housing. In this way the distance between the porous storagemedium and hence between the liquid storage portion and the pressureoutlet can be maximized. In embodiments wherein the pressure containerand its pressure housing comprise an elongated geometric structure, suchlike a tubular shape it is of particular benefit to arrange the pressureoutlet and the porous storage medium at oppositely located longitudinalor axial ends of the pressure housing.

In a further embodiment, the porous storage medium is arranged on abottom portion of the pressure housing and is held in place or issqueezed by a perforated grid. Typically, the porous storage medium israther elastic and may require interaction with at least one fixingmeans to keep it rigidly fastened to the pressure housing. A perforatedgrid typically comprises numerous perforations in order to allowevaporation of the liquid phase stored in the porous storage medium. Bymeans of the perforated grid, the porous storage medium may besandwiched between the bottom portion of the pressure housing and theperforated grid. The perforated grid may be engageable with an inside ofa sidewall portion of the pressure housing so as to fix the porousstorage medium to the bottom portion. It is conceivable that theperforated grid is positively engageable with at least one fixingelement or fixing structure located at the inside of the sidewallportion of the pressure housing. Alternatively, the perforated griditself may be subject to squeezing, e.g. by means of a closure of thepressure housing or by means of a distance ring operably engageable witha closure of the pressure housing.

It is even conceivable to provide and to modify the degree of squeezingof the porous storage medium by varying the pressure acting on theperforated grid. In this way, a medium pore size as well as the overallgeometric dimensions of the porous storage medium can be modified ingeneral in order to modify a gas pressure level at the pressure outlet.

In another embodiment, the pressure outlet is located in an outletmember releasably engageable with the pressure housing. The outletmember effectively serves as a closure to close the pressure housingwith regard to the exterior. The closure or outlet member is typicallyconnectable with a top portion of the pressure housing located oppositethe bottom portion thereof. In this way, the outlet member is inherentlylocated at a maximum distance from the porous storage medium arranged onthe opposite bottom portion. By means of a releasable or detachableoutlet member, the pressure container may be refilled if necessary.Alternatively, the pressure container may be designed and configured asa disposable device that is discarded in its entirety once the medicaldevice has been propelled by the driving medium.

In another embodiment, the outlet member comprises a sidewall threadedlyengageable with a correspondingly threaded sidewall portion of thepressure housing. In this way, the outlet member may exert or induce avariable squeezing pressure onto the porous storage medium. Depending onthe specific geometry of the outlet member, the pressure housing, theporous storage medium and/or of the perforated grid either a directmechanical contact between the sidewall of the outlet member and theperforated grid is conceivable or the pressure container is furtherequipped with a distance member arranged between the sidewall of theoutlet member and the perforated grid. Typically, the outercircumference of the outlet member's sidewall comprises an outer threadto mate and to engage with a correspondingly shaped inner thread of acorrespondingly shaped sidewall portion of the pressure housing. Atleast one of the sidewalls or sidewall portions of outlet member andpressure housing is typically provided with a seal, such like an O-ringin order to provide a gas tight sealing of the interior volume withrespect to the exterior. Additional or instead of an O-ring, a sealingtape may be wound along at least a portion of one of the threads of thesidewall of the pressure housing and the outlet member.

With the threaded engagement of the outlet member and the pressurehousing, variable pressures can be applied to the porous storage mediumin order to modify its liquid absorption capability and evaporationcharacteristics. A pressure acting on the porous storage medium can bearbitrarily and continuously modified by screwing or unscrewing theoutlet member into the pressure housing.

According to another embodiment, the porous storage medium extends alonga bottom portion and along a sidewall portion of the pressure housing.In other words, the porous storage medium extends almost along theentirety of the inward-facing portion of the pressure housing except aportion of the pressure housing located in direct vicinity to thepressure outlet. Given that the pressure housing is of elongated orcylindrical shape and that the pressure outlet is located at an upperlongitudinal end of the pressure housing, the bottom portion as well asthe sidewall portions of the pressure housing are, cladded, lined, orcoated with the porous storage medium. Arranging of the porous storagemedium to the inside of the wall structure of the pressure housinginherently provides a good thermal coupling to the exterior. If themedical device and/or its portable pressure container is, for instance,in thermal contact with the skin of a patient, evaporation enthalpy forthe evaporation of the liquid phase into the gas phase can be easilyextracted from the body heat.

The porous storage medium may provide a kind of a cladding at the insideof the pressure housing. With the porous storage medium extending alonga bottom portion and along a sidewall portion of the pressure housingthe gas storage portion of the interior volume is almost completelyenclosed by the liquid storage portion.

According to a further embodiment, the entirety of the inside of thepressure housing is provided or covered by the porous storage medium.The pressure outlet may then comprise a fluid channel extending throughand intersecting the porous storage medium so that one end of thepressure outlet is located inside the gas storage portion whereas anopposite end thereof is either accessible from outside or is locatedoutside the pressure housing.

According to another embodiment, the porous storage medium comprises aself-supporting elongated rod structure that is fixed with onelongitudinal end to the pressure housing and extends with an oppositelongitudinal end into the gas storage portion. A self-supportingelongated rod structure is sufficiently stable to extend into the gasstorage portion without getting in mechanical contact with the inside ofthe pressure housing. In other words, by means of a self-supportingelongated rod structure the porous storage medium can be exclusivelyfixed with only one end to the pressure housing while all other orresidual outside-facing surface portions of the porous storage mediumare located inside the gas storage portion thereby forming orconstituting a boundary between the liquid storage portion and gasstorage portion.

It is of particular benefit when the self-supporting elongated rodstructure is exclusively connected to a closure of the pressurecontainer. The closure is typically releasably attachable to thepressure housing to seal the interior volume thereof. By loosening andremoving the closure from and out of the pressure housing, the porousstorage medium fixed thereto can be taken out of the pressure housing.Such a configuration is of particular use for refilling of the pressurecontainer. The closure may serve as a handle to displace or to removethe porous storage medium. For instance, the porous storage medium maybe gripped by means of the closure and could be immersed into the liquiddriving medium to soak and to absorb driving medium. Thereafter, theporous storage medium and the closure can be inserted into and affixedto the pressure housing, thereby arranging the porous storage medium ata predefined position inside the interior volume.

In another embodiment, the pressure container comprises a fluid channelin flow connection with the pressure outlet. The fluid channel extendsfrom a sidewall portion of the pressure housing into the interior volumebut terminates with an inner end in the gas storage portion. The fluidchannel may be integrally formed with the pressure housing or may beprovided as a separate part. Typically, the inner end of the fluidchannel is located at a predefined distance to the sidewall as well asto a bottom or top portion of the pressure housing. Since the inner endof the fluid channel is located at a predefined distance from the wallstructure of the pressure housing it is possible to implement a dynamicboundary between the liquid storage portion and the gas storage portion.

Hence, the interior volume of the pressure housing may be only partiallyfilled with the liquid phase of the driving medium. But then the fillinglevel should be reduced to such a degree that the surface of the liquidphase cannot get into contact with the inner end of the fluid channelirrespective on any orientation of the pressure housing. Hence, for anyarbitrary orientation leading to different positions of the liquid phasethe inner end of the fluid channel will be located at least at apredefined distance to the surface of the liquid phase of the drivingmedium.

According to a further embodiment, the inner end of the fluid channel iscovered with a splash guard. In other words, as seen in longitudinaldirection the inner end of the elongated fluid channel is closed by thesplash guard. In order to provide ingress of the gas phase into thefluid channel the fluid channel has at least one inlet opening in asidewall portion. By making use of a splash guard at the inner end ofthe fluid channel ingress of the liquid phase of the driving medium intothe fluid channel can be effectively prevented, even in case that thepressure container should be subject to mechanical shock or vibrations.

Typically, the at least one or several inlet openings of the fluidchannel is or are arranged in the sidewall portion thereof in closevicinity to the splash guard or to the inner end of the fluid channel.In this way, it can be assured that only the gas phase will be able toenter the fluid channel even when the pressure container is orientedupside down.

According to another embodiment, the porous storage medium or poroustransport medium comprises at least one of a cotton wool, a spongematerial, a porous wick material or combinations thereof. The porousstorage medium may comprise a foamed structure. It may comprise orconsist of a polymeric or synthetic material. Alternatively, the porousstorage medium comprises or consists of a fiber material, a non-wovenmaterial or non-woven fabric.

The porous storage medium may be selected in accordance and in view ofthe driving medium. The porous storage medium may be selected on thebasis of its median pore size and with regard to the surface tension ofthe driving medium.

According to another embodiment, the liquid storage portion of theinterior of the portable pressure container is at least partially filledby a liquid phase of the driving medium. In particular, the pressurecontainer is prefilled with the driving medium to such an extent, thatthe interior of the pressure housing is filled by an equilibrium of theliquid phase and the gas phase of the driving medium. A prefilledpressure container is particularly suitable as a disposable pressurecontainer, which is intended to be discarded after use.

Certain aspects also relate to a pressure-driven portable medical devicecomprising a pressure-driven drive mechanism and comprising at least onepressure container as described above. Typically, the portable medicaldevice is configured as an injection device for intradermal orsubcutaneous injection of a liquid medicament. The medical device isparticularly adapted and configured for releasable adhesion to the skinof a patient. The pressure container provides a source of energy thatcan be used to induce or to trigger a fully automated injection processstarting with launching of a needle to penetrate or to pierce biologicaltissue, to optionally establish a fluid connection between an injectionneedle and a cartridge containing the liquid medicament, and to induceand to conduct injection of the liquid medicament into the biologicaltissue by a continuous or step-wise discharging of the medicament fromthe cartridge.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment, the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment, the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment, the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy, wherein in a further embodiment, thepharmaceutically active compound comprises at least one human insulin ora human insulin analogue or derivative, glucagon-like peptide (GLP-1) oran analogue or derivative thereof, or exendin-3 or exendin-4 or ananalogue or derivative of exendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins, which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (CH) and the variable region (VH). In onespecies, the constant region is essentially identical in all antibodiesof the same isotype, but differs in antibodies of different isotypes.Heavy chains γ, α and δ have a constant region composed of three tandemIg domains, and a hinge region for added flexibility; heavy chains μ andε have a constant region composed of four immunoglobulin domains. Thevariable region of the heavy chain differs in antibodies produced bydifferent B cells, but is the same for all antibodies produced by asingle B cell or B cell clone. The variable region of each heavy chainis approximately 110 amino acids long and is composed of a single Igdomain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, three onthe light (VL) and three on the heavy (VH) chain, are responsible forbinding to the antigen, i.e. for its antigen specificity. These loopsare referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H-H interchaindisulfide bond. F(ab')2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

The pressure container provides a rather constant pressure level of adriving medium during the entire duration of an injection procedure. Theportable pressure container is suitable for miniaturized medicaldevices, in particular to miniaturized injection devices that areintended to be carried along by a patient over a comparatively long timeinterval, such as several minutes or several hours. The portablepressure container provides a rather space-saving but also long-lastingsource of mechanical energy for a pressure driven or pressure propelledinjection device. Furthermore, the pressure container is easy tomanufacture with a high degree of reproducibility at moderate or lowcosts. Moreover, the pressure container is storable in a configurationready to use over a comparatively long time interval without asubstantive degradation or dissipation of energy stored therein.

It will be further apparent to those skilled in the art that variousmodifications and variations can be made to the present inventionwithout departing from the spirit and scope of the invention.

Further, it is to be noted, that any reference numerals used in theappended claims are not to be construed as limiting the scope of theinvention.

BRIEF DESCRIPTION OF THE FIGURES

In the following, embodiments of the drive mechanism and the injectiondevice are described in detail by making reference to the drawings, inwhich:

FIG. 1 is a cross section of one embodiment of the portable pressurecontainer,

FIG. 2 is a cross section of another embodiment of the pressurecontainer,

FIG. 3 is a cross section through a further embodiment of the pressurecontainer,

FIG. 4 is a cross section through another embodiment of the pressurecontainer,

FIG. 5 is a cross section through a further embodiment of the pressurecontainer and

FIG. 6 is a schematic illustration of a pressure-driven portable medicaldevice comprising a pressure container in accordance with one of theembodiments of FIGS. 1-5.

DETAILED DESCRIPTION

In FIG. 6, an injection device 20 is schematically illustrated. Itcomprises a housing 22, typically of tubular shape extending in an axialdirection (z). Inside the housing 22 there is arranged a cartridge 24comprising a tubular barrel 25 and being filled with a liquid medicament26. Near a distal end the housing 22 is provided with a needle assemblyhaving a cup-shaped needle hub and an injection needle 44 extending inlongitudinal or axial direction (z). In distal direction, the injectionneedle faces away from the injection device 20. With its distal end, theinjection needle 34 may penetrate or pierce biological tissue to deliverthe liquid medicament 26. With its opposite proximal end facing inproximal direction, the injection needle 44 is configured to penetrateand to puncture a seal 30 at the distal end of the cartridge 24. Theproximal end extends in proximal direction through an aperture of thedistal end of the housing 22.

In the proximal direction, near a proximal end 27, the cartridge 24 issealed by a piston 28 acting as a displaceable seal of the cartridge 24.The piston 28, typically of elastomeric material, such like a natural orsynthetic rubber is displaceable in distal direction in order to expel apredefined amount of the medicament 26 via the injection needle 44,typically at a predefined flow rate. The piston 28 comprises aproximally-facing thrust receiving surface 29, which is subject to anincreased pressure level. With the present injection device 20, apressurized medium, such as a pressurized fluid or gas enters theproximal side of the housing 22 to apply a driving pressure to thepiston 28.

For this, the housing 22 is in fluid connection or fluid communicationwith a pressure container 100 providing a medium, typically in form of apressurized gas. In order to control the velocity of displacement of thepiston 28 and to control the flow rate of the medicament 26 through theinjection needle 44 there is further provided a flow restrictor 50,schematically illustrated in FIG. 6. The flow restrictor 50 is locatedin the flow path between the pressure container 100 and the piston 28.The injection device 20 further comprises a gas propelled drivemechanism 70 with a drive member 60, located inside the housing 22proximal to the cartridge 24. The drive member 60 is in sealedengagement 62 with the inside of the sidewall of the housing 22. As soonas a pressurized gas enters the housing 22, the drive member in sealedengagement with the housing 22 will be urged in distal direction therebypushing the entire cartridge 24 in distal direction. Consequently, theseal 30 at the cartridge's distal end will be pierced by the proximaltip of the double tipped injection needle 44, thereby gaining access tothe interior of the cartridge 24. The cartridge has arrived in a distalend position inside the housing 22. In this configuration, the drivemember 60 will be susceptible for the driving medium to get therethroughso that the pressurized gas is then able to drive the piston 28 of thecartridge 24 in a well defined and controlled way. Thus, the piston 28moves in distal direction, thereby dispensing and expelling themedicament from the cartridge 24.

In FIGS. 1-5 various embodiments of pressure containers 100, 200, 300,400, 500 are illustrated that are capable to provide a rather constantgas flow at a pressure outlet 102, 202, 302, 402, 502 provided in apressure housing 101, 201, 301, 401, 501, wherein said pressure housingconfines an interior volume 103, 203, 303, 403, 503. The variouspressure containers 100, 200, 300, 400, 500 comprise a liquid storageportion 105, 205, 305, 405, 505 and a gas storage portion 104, 204, 304,404, 504. The liquid storage portion 105, 205, 305, 405, 505 isconfigured to store and to accommodate a liquid phase 15 of a drivingmedium 10 whereas the gas storage portion 104, 204, 304, 404, 504 isconfigured to store or to accommodate a gas phase 14 of the drivingmedium 10.

As shown in FIGS. 1-5 the pressure outlet 102, 202, 302, 402, 502 isonly or exclusively in flow connection or fluid communication with thegas storage portion 104, 204, 304, 404, 504 so that only the gas phase14 of the driving medium 10 will be able to emanate or to escape fromthe pressure housing 101, 201, 301, 401, 501 through the pressure outlet102, 202, 302, 402, 502.

In the various embodiments as shown in FIGS. 1-5, the pressure housing101, 201, 301, 401, 501 is of substantially cylindrical or cubicrectangular shape. However, the pressure housing is by no way limited tothe illustrated geometric forms. The pressure housing 101 could alsohave a spherical, oval or ellipsoidal shape. In the various embodimentsof FIGS. 1-5, the pressure housing 101, 201, 301, 401, 501 comprises abottom portion 107, 207, 307, 407, 507 and at least one sidewall 106,206, 306, 406, 506 extending towards a top portion 108, 208, 308, 408,508. In the illustrations according to FIGS. 1 and 2 the pressurecontainer 100, 200 is rotated by 90° so that it is lying on its sidewall106, 206.

The pressure container 100, as shown in FIG. 1, comprises a fluidchannel 110 in flow connection with the pressure outlet 102. The fluidchannel 110 extends inwardly from the top portion 108 of the pressurehousing 101 and into the interior 103 of the pressure housing 101. Thefluid channel 110 formed by a conically or cylindrically-shaped sidewall115 terminates at an inner end 112 that is located at a predefineddistance from the sidewall 106, as well as from the bottom portion 107and the top portion 108 of the pressure housing 101. The inner end 112of the fluid channel 110 is further covered by a splash guard 114 so asto prevent ingress of the liquid phase 15 of the driving medium 10 intothe fluid channel 110.

For the gas phase 14 to enter the fluid channel 110, there is providedat least one inlet opening 116 in the sidewall 115 of the fluid channel110. As shown in FIG. 1 there are provided at least two inlet openings116 that are located in direct vicinity to the splash guard 114 and thatare hence located near the inner end 112 of the fluid channel 110. Inthis way, the liquid phase 15 of the driving medium 10 can be storedinside the interior volume 103 without being fixed in a particularregion of the interior volume.

Hence, the boundary between the liquid phase 15 and the gas phase 14 ofthe driving medium 10 is of dynamic type and depends on the orientationof the portable pressure container 100 and the effect of the gravity onthe liquid phase 15. In this embodiment, the interior volume 103 is onlypartially filled with the liquid driving medium so that the fillinglevel of the liquid phase 15 never reaches or never gets in contact withthe inlet openings 116 of the fluid channel 110. For instance, in asubstantially vertical orientation, wherein the top part 108 is locatedon top and wherein the bottom portion 107 is a lower portion of thepressure housing 101, the filling level of the liquid phase 15 issmaller than the distance between the inner end 112 and the bottomportion 107.

In another orientation, in which the portable pressure container 100 isfor instance oriented upside down so that the pressure outlet 102 islocated at a lower portion, the filling level of the liquid phase 15will be smaller than the distance between the inlet opening 116 and thetop portion 108 of the pressure housing 101. In this way, it can beeffectively guaranteed, that only the gas phase 14 discharges from theinterior volume 103 irrespective of the momentary orientation of theportable pressure container 100.

Even though not particularly illustrated, the pressure outlets 102, 202,302, 402, 502 of all embodiments as illustrated in FIGS. 1-5, may beprovided with a standardized coupling or connector by way of which thepressure container 100, 200, 300, 400, 500 can be releasably connectedto the medical device 20, and in particular to a gas-propelled drivemechanism 70 of the medical device 20.

In the embodiment according to FIG. 2, a static configuration of theboundary between the liquid storage portion 205 and the gas storageportion 204 is illustrated. There, the gas storage portion 204 islocated in direct vicinity to the top portion 208 of the pressurehousing 202. It is separated and divided from the liquid storage portion205 by a division wall 220. The division wall 220 is intersected by aporous transport medium 210. The porous storage medium 210 comprises anelongated rod structure 214 and is only and exclusively fixed to thepressure container 201 at the division wall 220. The portion where therod structure 214 is connected to and intersects the division wall 220acts as an evaporation chamber 212. The residual portion of the rodstructure 214 is located inside the liquid storage portion 205. In thisembodiment, the liquid storage portion 205 may be completely or almostcompletely filled with the liquid phase 15 of the driving medium 10. Theporous transport medium 210 has pores of a particular size so that theliquid phase 15 of the driving medium 10 is continuously transportedtowards and into the evaporation chamber 212 through the capillaryforces that arise due to the surface tension of the liquid phase 15 andthe pore size of the porous transport medium 210.

The porous transport medium 210 is illustrated as a self-supportingelongated rod structure 214, which is only fixed with one longitudinalend 215 to the pressure housing 201 while an opposite longitudinal end216 extends into the gas storage portion 204. Having a self-supportingand rather inflexible rod structure 214 is somewhat beneficial to assurethat the porous transport medium 210 does not adhere to the inside ofthe sidewall 206 of the pressure housing 201. However, it is alsoconceivable that the porous transport medium 210 is of flexible type. Itmay comprise a natural or synthetic wick material to providetransportation of the liquid phase towards the evaporation chamber 212.

In a further embodiment of the portable pressure container 300 as shownin FIG. 3, there is provided a porous storage medium 310 that isarranged along the inside of the pressure housing 301. As shown in thecross section according to FIG. 3 the porous storage medium 310 entirelycovers the bottom portion 307 as well as the sidewall or sidewallportions 306 of the pressure housing 301. It may even abut with the topportion 108 in direct vicinity to the sidewalls 106. Only the region orthe vicinity of the pressure outlet 302 is free of the porous storagemedium 310.

In this way, the gas storage portion 304 is almost completely enclosedby the liquid storage portion 305. The boundary between the gas storageportion 304 and the liquid storage portion 305 is static and isdetermined by the geometric dimensions of the porous storage medium 310.The arrangement of the porous storage medium 310 to the sidewall 306 andto the bottom portion 307 is beneficial for a thermal coupling of theliquid storage portion 105 to the exterior. When establishing forinstance a thermal coupling between the pressure housing 310 and theskin of a patient, evaporation enthalpy for a continuous transfer of theliquid phase 15 into the gas phase 14 during use of the pressurecontainer 300 can be extracted from the body heat.

In the embodiments as shown in FIGS. 3, 4, and 5, the liquid storageportion 305, 405, 505 is defined by the geometric dimensions of theporous storage medium 310, 410, 510. Typically, the porous storagemedium 310, 410, 510 may comprise or consist of a cotton wool, a spongematerial, a porous wick material, as well as variable natural orsynthetic porous media exhibiting a pore size and a pore volume or poredensity to maximize the storage capability of the liquid phase pervolume.

In the further embodiment as shown in FIG. 4, the porous storage medium410 is connected to a closure 412 that is configured to be releasablyattached to the bottom portion 407 of the pressure housing 401. Here,the porous storage medium 410 comprises a self-supporting rod structure414 extending into the interior volume 403 confined by the pressurehousing 401. Besides a contact with the bottom portion 407 and a contactwith the closure 412, the porous storage medium 410 is totallycontactless to the inside of the pressure housing 401. Hence, FIG. 4represents an inverted configuration compared to the embodiment as shownin FIG. 3. Here, the gas storage portion 404 almost completely surroundsthe liquid storage portion 405 that is defined by the geometricdimensions of the porous storage medium 410. The rod structure 414 ofthe porous storage medium 410 is connected with one longitudinal end 415to the closure 412 whereas an opposite longitudinal end 416, hence thefree end 416 of the rod structure 414, is located inside the interiorvolume 403 of the pressure housing 401. It is located at a predefineddistance from the top portion 408 of the pressure housing 401 for nothindering the flow of the gas phase towards the pressure outlet 402.

The closure 412 may be of releasable or detachable type. It may be forinstance threadedly engageable with the bottom 407 of the pressurehousing 401. At least one of the closure 412 or the pressure housing 401comprises a seal 418, typically in form of an O-ring, in order toprovide a leak-proof closure assembly. The embodiment as shown in FIG.4, is particularly suitable to provide a refill of the portable pressurecontainer 400. By detaching and removing the closure 412, the porousstorage medium 410 is detachable from the interior volume 403. It may beimmersed in a liquid phase 15 of the driving medium 10 to saturate theporous storage medium 410. Thereafter, the porous storage medium 410 maybe re-inserted into the interior volume 403 and the closure 412 may sealthe pressure housing 401.

The further embodiment as shown in FIG. 5, comprises a cup-shapedpressure housing 501 having an interior volume 503 that is delimited andconfined by a planar-shaped bottom portion 507 and a cylindricalsidewall 506. An upper portion of the inside of the cylindrical sidewall506 is provided with an inner thread 516 to threadedly engage with anouter thread 515 of an outlet member 512 comprising the pressure outlet502. The pressure outlet 502 is further provided with an outlet valve520, which may be implemented as a commercially available ball valve orthe like.

The cup-shaped pressure housing is closed by the outlet member 512. Thecylindrically-shaped sidewall 514 of the outlet member 512 is configuredto match with the inner diameter of the sidewall 506 of the pressurehousing 501 to establish a threaded and releasable connection of thecup-shaped pressure housing 501 and the outlet member 512. Inside thepressure housing 501, there is provided a porous storage medium 510covering the entirety of the planar-shaped bottom portion 507. On top ofthe porous storage medium 510, there is provided and positioned aperforated grid 511 having numerous perforations 511 a that allowevaporation of the liquid phase 15 into the gas phase 14. The perforatedgrid 511 provides mechanical stability to the porous storage medium 510and keeps the porous storage medium 510 in place at the bottom portion507.

There is further provided a distance member 518 or spacer that has anouter circumference that matches with the inner circumference of thesidewall 506 of the cup-shaped pressure housing 501. An upper portion ofthe distance member 518 is in axial abutment with a lower face of theoutlet member 512. In this way, the outlet member 512 is mechanicallyengageable with the perforated grid 511 as well as with the porousstorage medium 510. By screwing the outlet member 512 further into thecup-shaped pressure housing 501, a pressure can be applied to theperforated grid 511 and to the porous storage medium 510 via thedistance member 518.

Typically and in order to provide a sufficient sealing effect, thethreaded engagement between outer thread 515 of the outlet member 512and the inner thread 516 of the sidewall 506 is provided with a sealingtape, e.g. of polytetrafluoroethylene (PTFE). The cup-shaped pressurehousing 501, as well as the pressure housings 101, 201, 301, 401, maycomprise a transparent material, such like polycarbonate or similarplastic but durable materials that allow visual inspection of theinterior of the portable pressure container 100, 200, 300, 400, 500.

The size of the perforations 511 a of the perforated grid 511 may be ina range of 1 or 2 mm so as to provide sufficient mechanical stability tothe porous storage medium 510 and to allow a sufficient evaporation rateand a respective gas flow from the liquid phase 15 towards the gas phase14.

The distance member 518 may comprise a piece of a hose and theperforated grid 511 may comprise a plastic material, which may either beinjection molded, cut or punched to provide a desired perforatedstructure.

The driving medium may comprise a haloalkane such liketetrafluoromethane or similar driving media. For instance, the drivingmedium may comprise or consist of 1,1,1,2-tetrafluoroethane, alsodenoted as R134a. Likewise, also 2,3,3,3-tetrafluoropropene, alsodenoted as HFO-1234yf and mixtures thereof with at least one of theaforementioned driving medias can be used as the driving medium. Thesedriving medias are gaseous at room temperature but may easily undergo aphase transition to the liquid phase if sufficiently pressurized orheated.

LIST OF REFERENCE NUMBERS

-   10 driving medium-   14 gas phase-   15 liquid phase-   20 medical device-   22 housing-   24 cartridge-   25 barrel-   26 medicament-   27 proximal end-   28 piston-   29 thrust receiving surface-   30 seal-   44 injection needle-   50 flow restrictor-   60 drive member-   62 sealed engagement-   70 drive mechanism-   100 pressure container-   101 pressure housing-   102 pressure outlet-   103 interior volume-   104 gas storage portion-   105 liquid storage portion-   106 sidewall-   107 bottom portion-   108 top portion-   110 fluid channel-   112 inner end-   114 splash guard-   115 sidewall-   116 inlet opening-   200 pressure container-   201 pressure housing-   202 pressure outlet-   203 interior volume-   204 gas storage portion-   205 liquid storage portion-   206 sidewall-   207 bottom portion-   208 top portion-   210 porous transport medium-   212 evaporation chamber-   214 rod structure-   215 longitudinal end-   216 longitudinal end-   220 division wall-   300 pressure container-   301 pressure housing-   302 pressure outlet-   303 interior volume-   304 gas storage portion-   305 liquid storage portion-   306 sidewall-   307 bottom portion-   308 top portion-   310 porous storage medium-   400 pressure container-   401 pressure housing-   102 pressure outlet-   403 interior volume-   404 gas storage portion-   405 liquid storage portion-   406 sidewall-   407 bottom portion-   408 top portion-   410 porous storage medium-   412 closure-   414 rod structure-   415 longitudinal end-   416 longitudinal end-   418 seal-   500 pressure container-   501 pressure housing-   502 pressure outlet-   503 interior volume-   504 gas storage portion-   505 liquid storage portion-   506 sidewall-   507 bottom portion-   508 top portion-   510 porous storage medium-   511 perforated grid-   511 a perforation-   512 outlet member-   514 sidewall-   515 outer thread-   516 inner thread-   518 distance member-   520 outlet valve

1. A portable pressure container for driving a medical device, thecontainer comprising: a pressure housing defining an interior volume,the interior volume of the pressure housing comprising a liquid storageportion configured to store a liquid phase of a driving medium and a gasstorage portion configured to store a gas phase of the driving medium,the liquid storage portion and the gas storage portion being in flowconnection with each other; and a pressure outlet extending through thepressure housing, the pressure outlet being in direct flow connectionwith the gas storage portion of the interior volume and not the liquidstorage portion of the interior volume.
 2. The pressure containeraccording to claim 1, wherein only the gas storage portion of theinterior volume of the pressure housing is in direct flow connectionwith the pressure outlet.
 3. The pressure container according to claim1, wherein the liquid storage portion is at least partially filled by aliquid phase of the driving medium and wherein the liquid phase of thedriving medium is free to evaporate into the gas storage portion.
 4. Thepressure container according to claim 3, wherein a volume of the liquidphase of the driving medium is less than about 60% of the interiorvolume.
 5. The pressure container according to claim 3, furthercomprising a fluid channel having an inner end that extends into the gasstorage portion, wherein a surface of the liquid phase of the drivingmedium is separated from the inner end of the fluid channel in anyorientation of the pressure container.
 6. The pressure containeraccording to claim 1, wherein the pressure housing comprises: a bottomportion; a top portion; and at least one sidewall portion extending fromthe bottom portion towards the top portion.
 7. The pressure housingaccording to claim 6, further comprising a fluid channel in flowconnection with the pressure outlet, the fluid channel extending fromone of the top portion, the sidewall portion, or the bottom portion ofthe pressure housing, into the interior volume.
 8. The pressurecontainer according to claim 7, wherein the fluid channel comprises aninner end arranged in the gas storage portion.
 9. The pressure containeraccording to claim 8, wherein the inner end of the fluid channel isarranged at a predefined distance from the sidewall portion and at apredefined distance from at least one of the bottom portion and the topportion.
 10. The pressure container according to claim 8, wherein in avertical orientation of the pressure housing, in which the pressureoutlet and the top portion are located on top and in which the bottomportion of the pressure housing is a lower portion of the pressurehousing, a filling level of the liquid phase of the driving mediumcontained in the interior volume is smaller than a distance between theinner end of the fluid channel and the bottom portion.
 11. The pressurecontainer according to claim 8, wherein in an upside down orientation ofthe pressure housing, in which the pressure outlet is located at a lowerportion, a filling level of the liquid phase of the driving mediumcontained in the interior volume is smaller than a distance between theinner end of the fluid channel and the top portion.
 12. The pressurecontainer according to claim 8, wherein the inner end of the fluidchannel is covered by a splash guard.
 13. The pressure containeraccording to claim 7, wherein the fluid channel comprises a sidewallportion, wherein the sidewall portion comprises at least one inletopening at or near an inner end of the fluid channel, wherein the innerend of the fluid channel is located in the gas storage portion.
 14. Thepressure container according to claim 7, wherein the fluid channel isintegrally formed with the pressure housing.
 15. The pressure containeraccording to claim 7, wherein the fluid channel is separate from thepressure housing and is connected to at least one of the pressureoutlet, the top portion, the sidewall portion or the bottom portion. 16.The pressure container according to claim 1, wherein the pressurehousing has a cylindrical shape, a cubic shape, a rectangular shape, aspherical shape, an oval shape or an ellipsoidal shape.
 17. The pressurecontainer according to claim 1, wherein the interior volume of thepressure housing is divided between the liquid storage portion and thegas storage portion.
 18. The pressure container according to claim 1,wherein the driving medium is disposed in the interior volume of thepressure housing, wherein the liquid storage portion is completelyfilled by the liquid phase of the driving medium and wherein the gasstorage portion is completely filled by the gas phase of the drivingmedium.
 19. A pressure driven portable medical device comprising: apressure driven drive mechanism; and at least one portable pressurecontainer, the pressure container comprising: a pressure housingdefining an interior volume, the interior volume of the pressure housingcomprising a liquid storage portion configured to store a liquid phaseof a driving medium and a gas storage portion configured to store a gasphase of the driving medium, the liquid storage portion and the gasstorage portion being in flow connection with each other; and a pressureoutlet extending through the pressure housing, the pressure outlet beingin direct flow connection with the gas storage portion of the interiorvolume and not the liquid storage portion of the interior volume. 20.The pressure driven portable medical device according to claim 19,wherein the interior volume of the pressure housing is divided betweenthe liquid storage portion and the gas storage portion.